Stem cells (SCs) have been widely characterized as precursors that self-replicate with the ability to give rise to one or more cell types, known as potency. Stem cells can be hierarchically classified as unipotent, multipotent, pluripotent and totipotent. Unipotent stem cells can produce only one cell type (e.g. neurons), whereas multipotent ones can differentiate into several cell types (e.g. hematopoietic stem cells, HSCs). An embryonic stem cell (ESC), derived from the inner cell mass (ICM) of the embryo is pluripotent as it can differentiate into cells of three germ layers, but not into trophoblastic cells, whereas the zygote is totipotent as it produces cells of embryonic as well as extra-embryonic tissue. On the other hand, SCs also can be isolated from a variety of adult tissues sources such as bone marrow, skin, adipose tissues and many more. However, these sources pose limitations which include lack of starting material, invasive procurement procedures, tedious processing techniques and most importantly, limited proliferative capacity due to their adult origin.
Another source originating from extra-embryonic tissue is Wharton's jelly (WJ) of human umbilical cord which has gained popularity due to its non-controversial source and abundance in mesenchymal stem cells (MSC) population from its raw starting material as disclosed by McGuirk and Weiss, in Placenta, vol. 32, pages S304-10 (2011). Further, WJ-MSCs share many properties with adult mesenchymal stem cells originated from bone marrow (BM-MSCs), but are generally considered as a more primitive population than the latter. In fact, while they possess several characteristics of ESCs, they do not form teratomas upon transplantation and their research does not raise ethical or legal issues. All these features open attractive perspectives for the propagation and engineering of WJ-MSCs for cell-based therapies.
In addition, they are also relatively easy to harvest and to process as compared to bone marrow or embryonic origin prior to ex vivo expansion as testified by C. C. Yang et al, in Plos One, vol. 3, doi: 10.1371/journal.pone.0003336 (2008). Another advantage of this source is that these cells have high proliferation rates, wide multi-potency, hypo-immunogenicity, do not induce tumorigenesis and have anti-tumor properties as claimed by C. Y. Fong et al, in Stem Cell Reviews, vol. 7, pages 1 to 16 (2011).
The potential of WJ-MSC was comprehensively investigated in which exposure towards exogeneous growth factors has shown to contribute to the formation of pre-chodrocytes cells as described in U.S. Pat. No. 5,919,702 by Purchio et al. Further work to obtain enriched osteoprogenitor cells from Wharton's Jelly was conducted by Davies et al., in their U.S. Patent application 2005/0148074. Recently, Majumdar in WO2012131618 A1 has described the method of obtaining pooled WJ-MSCs for the purpose of producing an off-the-shelf product. This was meant to serve as allogeneic MSC product for therapeutics application in large scale. Though the idea is noteworthy, it should also be noted that genetic variability among donors is a confounding factor that requires serious attention.
Though the allogeneic MSC that are being used in the transplantation have been thoroughly checked for human leukocyte antigen (HLA) markers, any variation especially in terms of genetic that may occur during the course of transplantation would be very difficult to identify and subsequently control. In addition, having a pooled cell culture has another disadvantage as it might contribute to graft versus host disease in certain recipients thus requiring rigorous follow-up sessions which would be unnecessary if the cells were to have propagated from a single donor. On the other hand, among the benefits of using cells isolated from single donor are reduced disease transmission, reduced alloimmunization and superior function and storage characteristics.
Taking into consideration of all these hurdles, the present disclosure relates to a composition comprising of large scale expansion of WJ-MSC from a single donor for the purpose of allogeneic transplantation.